Reversible Control of DNA Binding with Cucurbit[8]uril-Induced Supramolecular 4,4′-Bipyridinium–Peptide Dimers

Novo, Paula; García, Marcos D.; Peinador, Carlos; Pazos, Elena

doi:10.1021/acs.bioconjchem.1c00063

Cited by 10 publications

(8 citation statements)

References 42 publications

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“…Several studies have harnessed the host-guest chemistry of CB [7] to control the structures and functions of nucleic acids. 48,[51][52][53][54][55] However, to the best of our knowledge, this is the first report demonstrating gene expression control in a CFE system by the host-guest chemistry of CB [7]. Noteworthily, our system enabled the programming of the magnitude and rate of gene expression by selecting suitable guest structures involved in the host-guest interaction.…”

Section: Discussionmentioning

confidence: 99%

Reversible control of gene expression by guest-modified adenosines in a cell-free system via host–guest interaction

Okamura,

Yao,

Nagatsugi

2024

Preprint

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Gene expression technology has become an indispensable tool for elucidating biological processes and developing bio-technology. Cell-free gene expression (CFE) systems offer a fundamental platform for gene expression-based technology, in which the reversible and programmable control of transcription can expand its use in synthetic biology and medicine. This study shows that CFE can be controlled via the host–guest interaction of cucurbit[7]uril (CB[7]) with N6-guest-modified adenosines. These adenosine derivatives were conveniently incorporated into the DNA strand by a post-synthetic approach and formed a selective and stable base pair with complementary thymidine in DNA. Meanwhile, alternate addition of CB[7] and the exchanging guest molecule induced the reversible formation of a duplex structure through the formation and dissociation of a bulky complex on DNA. The kinetics of the reversibility were fine-tuned by changing the size of the modified guest moieties. When incorporated into a specific region of the T7 promoter sequence, the guest-modified adenosines enabled the tight and reversible control of in vitro transcription and protein expression in the CFE system. The present study marks the first utility of the host-guest interaction for the gene expression control in the CFE system, opening new avenues for developing DNA-based technology, particularly for precise gene therapy and DNA nano-technology.

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Section: Discussionmentioning

confidence: 99%

Reversible control of gene expression by guest-modified adenosines in a cell-free system via host–guest interaction

Okamura,

Yao,

Nagatsugi

2024

Preprint

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“…The addition of cucurbit [8]uril mediated heterodimerization of CFP-Np with YFP-MV, resulting in an energy transfer from donor CFP to acceptor YFP ( Uhlenheuer et al, 2011b ). Incorporation of a 4,4′-bipyridinium scaffold at the C-teminus of transcription factor (GCN4) opened up a new approach to the supramolecular control of peptide assemblies ( Novo et al, 2021 ). Cucurbit [8]uril-induced GCN4 dimerization by the formation of a homoternary supramolecular complex (1 cucurbit[8]uril:2 bipyridinium) could specifically bind to its targeted double-strand DNA.…”

Section: Dimerization Of Protein Via Molecular Chemistrymentioning

confidence: 99%

Molecular Approaches to Protein Dimerization: Opportunities for Supramolecular Chemistry

Đặng

2022

Front. Chem.

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Protein dimerization plays a key role in many biological processes. Most cellular events such as enzyme activation, transcriptional cofactor recruitment, signal transduction, and even pathogenic pathways are significantly regulated via protein-protein interactions. Understanding and controlling the molecular mechanisms that regulate protein dimerization is crucial for biomedical applications. The limitations of engineered protein dimerization provide an opportunity for molecular chemistry to induce dimerization of protein in biological events. In this review, molecular control over dimerization of protein and activation in this respect are discussed. The well known molecule glue-based approaches to induced protein dimerization provide powerful tools to modulate the functionality of dimerized proteins and are shortly highlighted. Subsequently metal ion, nucleic acid and host-guest chemistry are brought forward as novel approaches for orthogonal control over dimerization of protein. The specific focus of the review will be on host-guest systems as novel, robust and versatile supramolecular approaches to modulate the dimerization of proteins, using functional proteins as model systems.

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“…However, aromatic residues do not need to be present in the peptide sequence to achieve a high binding affinity, as shown for methionine‐terminated peptides [19] . The cucurbit[8]uril host is sufficiently large to bind two amino acid side chains simultaneously [20–23] . For instance, CB8 recognises the tripeptides Phy‐Gly‐Gly, Trp‐Gly‐Gly, [24–26] and Tyr‐Leu‐Ala [27] in aqueous buffers with high sequence specificity.…”

Section: Introductionmentioning

confidence: 99%

“…[19] The cucurbit [8]uril host is sufficiently large to bind two amino acid side chains simultaneously. [20][21][22][23] For instance, CB8 recognises the tripeptides Phy-Gly-Gly, Trp-Gly-Gly, [24][25][26] and Tyr-Leu-Ala [27] in aqueous buffers with high sequence specificity. These sequence preferences were already employed in the formation of supramolecular assemblies for sequestering, antibacterial activity, bioimaging, drug delivery, and tissue engineering.…”

Section: Introductionmentioning

confidence: 99%

Cucurbit[7]uril‐mediated Histidine Dimerization: Exploring the Structure and Binding Mechanism

Zaorska,

Malinska

2023

Chemistry A European J

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Cucurbit[7,8]urils are known to form inclusion complexes with hydrophobic amino acids such as Trp, Tyr, Phe, and Met, as well as peptides containing these residues at the N‐terminus. Despite their widespread use in protein purification, the affinity of histidine (His) for cucurbit[7,8]urils has not been extensively explored. In this study, X‐ray diffraction experiments were conducted to investigate the binding of two histidine moieties to the cucurbit[7]uril (CB7) cavity, resulting in a network of π–π and hydrogen bonds. This assembly was found to induce a His pKa shift of ΔpKa=−4. Histidine weakly bound to CB7 or CB8; however, isothermal titration calorimetry revealed micromolar equilibrium dissociation constant values for CB7 and CB8 when bound to dipeptides containing His at the C‐terminus. Conversely, dipeptides with His at the N‐terminus exhibited millimolar values. Additionally, the His‐Gly‐Gly tripeptide formed a 2 : 1 complex with CB7. These findings suggest the potential use of histidine and histidine‐containing tags in conjunction with CB7 for various biological applications.

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Reversible Control of DNA Binding with Cucurbit[8]uril-Induced Supramolecular 4,4′-Bipyridinium–Peptide Dimers

Cited by 10 publications

References 42 publications

Reversible control of gene expression by guest-modified adenosines in a cell-free system via host–guest interaction

Reversible control of gene expression by guest-modified adenosines in a cell-free system via host–guest interaction

Molecular Approaches to Protein Dimerization: Opportunities for Supramolecular Chemistry

Cucurbit[7]uril‐mediated Histidine Dimerization: Exploring the Structure and Binding Mechanism

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